Regulation of Cortical Actin Networks in Cell Migration Shiro Suetsugu and Tadaomi Takenawa Department of Biochemistry, Institute of Medical Science, University of Tokyo, and CREST, Japan Science and Technology Corporation (JST), 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan The actin cytoskeleton is a primary determinant of cell shape and motility. Studies on actin regulatory proteins are now coupled with studies of the signal transduction that directs actin cytoskeleton reorganization, and we have gained insights into how external stimuli such as chemoattractants drive changes in actin cytoskeleton. Chemoattractants regulate actin regulatory proteins such as the Arp2/3 complex through WASP family proteins, ADF/cofilin downstream of LIM-kinase, and various other phosphoinositide-dependent or -independent pathways. Through branching of actin filaments, Arp2/3 complex-dependent actin polymerization is suffcient to generate the force necessary for protrusion. KEY WORDS: Actin, Arp2/3 complex, WASP, N-WASP, WAVE, Cell motility. ß 2003 Elsevier Inc. I. Introduction When cells move toward a chemoattractant, extensive change in the cell shape must occur. Cells form protrusive structures such as filopodia, which are the spikes that protrude from the cell membrane, and leading edge lamellipodia, which are membrane protrusions associated with ruZing or waving of the cell membrane. These two types of structures elongate toward the chemoattractant. In contrast, on the side of the cell opposite to the chemoattractant, cell membrane retracts to shift the entire cell body. These coordinated changes in cell shape are the basis of cell migration (Abercrombie et al., 1970a,b,c, 1971, 1972). International Review of Cytology, Vol. 229 245 Copyright 2003, Elsevier Inc. 0074-7696/03 $35.00 All rights reserved.